Positive transcription elongation factor b (P‐TEFb), which comprises cyclin‐dependent kinase 9 (CDK9) kinase and cyclin T subunits, is an essential kinase complex in human cells. Phosphorylation of the negative elongation factors by P‐TEFb is required for productive elongation of transcription of protein‐coding genes by RNA polymerase II (pol II). In addition, P‐TEFb‐mediated phosphorylation of the carboxyl‐terminal domain (CTD) of the largest subunit of pol II mediates the recruitment of transcription and RNA processing factors during the transcription cycle. CDK9 also phosphorylates (...) p53, a tumor suppressor that plays a central role in cellular responses to a range of stress factors. Many viral factors affect transcription by recruiting or modulating the activity of CDK9. In this review, we will focus on how the function of CDK9 is regulated by viral gene products. The central role of CDK9 in viral life cycles suggests that drugs targeting the interaction between viral products and P‐TEFb could be effective anti‐viral agents. (shrink)

Some commentators argue that conception constitutes the onset of human personhood in a metaphysical sense. This threshold is usually invoked as the basis both for protecting zygotes and embryos from exposure to risks of death in clinical research and fertility medicine and for objecting to abortion, but it also has consequences for certain religious perspectives, including Catholicism whose doctrines directly engage questions of personhood and its meanings. Since more human zygotes and embryos are lost than survive to birth, conferral of (...) personhood on them would mean – for those believing in personal immortality – that these persons constitute the majority of people living immortally despite having had only the shortest of earthly lives. For those believing in resurrection, zygotes and embryos would also be restored to physical lives. These outcomes do not mean that conception cannot function as a metaphysical threshold of personhood, but this interpretation carries costs that others do not. For example, treating conception as a moral threshold of respect for human life in general, rather than as a metaphysical threshold of personhood, would obviate the prospect of the afterlife being populated in the main by persons who have never lived more than a few hours or days. (shrink)

The value of extending the human lifespan remains a key philosophical debate in bioethics. In building a case against the extension of the species-typical human life, Nicolas Agar considers the prospect of transforming human beings near the end of their lives into Galapagos tortoises, which would then live on decades longer. A central question at stake in this transformation is the persistence of human consciousness as a condition of the value of the transformation. Agar entertains the idea that consciousness could (...) persist in some measure, but he thinks little is to be gained from the transformation because the experiences available to tortoises pale in comparison to those available to human beings. Moreover, he thinks persisting human consciousness and values would degrade over time, being remade by tortoise needs and environment. The value available in the transformation would not, then, make the additional years of life desirable. Agar’s account does not, however, dispose of the tortoise transformation as a defensible preference. Some people might still want this kind of transformation for symbolic reasons, but it would probably be better that no continuing human consciousness persist, since that consciousness would be inexpressible as such. Even so, it is not irrational to prefer various kinds of lifespan extension even if they involve significant modifications to human consciousness and values. (shrink)

ABSTRACT In this essay the argument set forth by Michael Levin regarding the abnormality of homosexual behaviour is reviewed and criticized. Against his argument which holds that homosexual behaviour is abnormal because it constitutes an evolutionary aberration, I argue that Levin's and all similarly constructed arguments fail to show that evolutionary origins of sexual behaviour have any significant normative force. I contend that his notion of homosexuality is confused and that he fails to consider alternative methods of how homosexuality might (...) have indeed served evolutionary adaptive purposes or been the result of surplus adaptations. I argue, too, that Levin's linking of unhappiness with homosexual behaviour is spurious and ill‐supported. Consequently, I reject Levin's claims that public policy ought to do what it can to minimize the incidence of such behaviour. I argue by contrast that if happiness is the end of public policy decisions, then society ought to take what measures it can to protect persons in respect of their homosexual behaviour and identities. (shrink)

Reports about possible genetic bases of homoerotic sexual orientation in adults have received a kind of schizophrenic social reception. On the one hand, these reports have been welcomed by some gay men and lesbians as biological confirmation of the commonly held view that sexual orientation is an involuntary trait, that sexual orientation is not in any meaningful sense chosen. Simon LeVay has received mail from thankful correspondents who welcomed his 1991 report about the possible neuroanatomical basis for male homoerotic sexual (...) orientation, and some legal analysts see important implications of biological studies for the ways in which civil rights are recognized, especially those that depend on an immutable characteristic like race or gender. (shrink)

Medical residency—specialty training after the completion of medical school—is an essential component of medical education and is required in order to be a licensed, independent medical practitioner in most jurisdictions. As things currently stand in the United States, the match between medical school graduates and residency programs is governed by a match between rank-order lists prepared by candidates and residencies alike. An applicant picks a number of residency programs and ranks them according to order of interest. The residency program prepares (...) a similar list, ranking the candidates it most wants in its program. A computer program compares the rankings and makes assignments according to a certain algorithm. Using these lists, the match system assigns approximately 24,000 applicants to approximately 21,000 training positions in pediatrics, obstetrics and gynecology, internal medicine, and the rest. These assignments are then announced to all parties on specific days. The system has been in place since 1952 and is overseen by the National Residency Match Program, a nonprofit organization. This system has several advantages. First of all, it standardizes the timetable for decisions, and applicants are in no position to tie up offers while waiting to hear from other institutions. Institutions are not held captive, either, in making assignments while waiting to hear from particular parties. (shrink)

Carson Strong has argued that if human cloning were safe it should be available to some infertile couples as a matter of ethics and law. He holds that cloning by somatic cell nuclear transfer should be available as a reproductive option for infertile couples who could not otherwise have a child genetically related to one member of the couple. In this analysis, Strong overlooks an important category of people to whom his argument might apply, couples he has not failed to (...) consider elsewhere. In this discussion, however, Strong refers exclusively to opposite sex couples facing obstacles such as surgically removed ovaries and the inability to produce sperm. In fact, however, there are many adult couples who, while fertile in and of themselves, are not fertile as couples. This group includes not only opposite sex couples but coupled same sex partners as well. I believe the defenses Strong offers regarding the use of SCNT by opposite sex infertile couples would extend to same sex couples for two reasons. First, some same sex couples might face the inability to have a genetically related child, and second, Strong's arguments ultimately ground a general defense of SCNT independent of the question of a couple's fertility. (shrink)

For many commentators in bioethics and the law, safety is the fulcrum for evaluating the ethics of human reproductive cloning. Carson Strong has argued that if cloning were effective and safe it should be available to married couples who have tried to have children through various assisted reproductive technologies but been unable to do so. On his view, cloning should be available only as reproductive last resort. I challenged that limited use by trying to show that the arguments Strong adduces (...) in favor of reproductive somatic nuclear transfer for married couples extend to same-sex couples as well, who face a different kind of infertility. I also went on to argue that his justifications would in fact extend the legitimate use of SNT to any couples regardless of whether they had fertility difficulties or not. (shrink)

Spontaneous abortion is rarely addressed in moral evaluations of abortion. Indeed, 'abortion' is virtually always taken to mean only induced abortion. After a brief review of medical aspects of spontaneous abortion, I attempt to articulate the moral implications of spontaneous abortion for the two poles of the abortion debate, the strong pro-abortion and the strong anti-abortion positions. I claim that spontaneous abortion has no moral relevance for strict pro-abortion positions but that the high incidence of spontaneous abortion is not (as (...) some claim) eo ipso any sort of justification for voluntarily induced abortion. Secondly, I show that if the strict anti-abortionist position is to be taken seriously in its insistence that prenatal life has a right to be protected by virtue of its being conceived, then it seems necessary to take measures to prevent spontaneous abortion and its presumptive causes, and this as a matter of moral obligation. (shrink)

Some commentators indirectly challenge the ethics of using synthetic gametes as a way for same-sex couples to have children with shared genetics. These commentators typically impose a moral burden of proof on same-sex couples they do not impose on opposite-sex couples in terms of their eligibility to have children. Other commentators directly raise objections to parenthood by same-sex couples on the grounds that it compromises the rights and/or welfare of children. Ironically, the prospect of synthetic gametes neutralises certain of these (...) objections, insofar as they would ensure that children have parents whom they can know as their genetic parents, which outcome is not always possible when same-sex couples involve third parties as the source of gametes or embryos. Not all commentators in bioethics throw the use of synthetic gametes into doubt as far as same-sex couples are concerned, but even these commentators put parenting by gay men and lesbians at the conclusion of an argument rather than presupposing parental legitimacy from the outset. Synthetic gametes do raise questions of ethics in regard to parenthood for gay men and lesbians, but these are largely questions of access and equity, not questions of parental fitness and/or child welfare. (shrink)

H. Tristram Engelhardt has said that “in the 1960s and 1970s... religious bioethics fell into the shadow of established secular bioethics. I don't think that religious bioethics has ever really...

Some commentators have criticized bioethics as failing to engage religion both as a matter of theory and practice. Bioethics should work toward understanding the influence of religion as it represents people's beliefs and practices, but bioethics should nevertheless observe limits in regard to religion as it does its normative work. Irreligious skepticism toward religious views about health, healthcare practices and institutions, and responses to biomedical innovations can yield important benefits to the field. Irreligious skepticism makes it possible to raise questions (...) that otherwise go unasked and to protect against the overreach of religion. In this sense, bioethics needs a vigorous irreligious outlook every bit as much as it needs descriptive understandings of religion. (shrink)

Professional standards in medicine and psychology treat concurrent sexual relationships with patients as violations of fiduciary trust, and they sometimes rule out sexual relationships even after a clinical relationship is over. These standards also rule out sex with research subjects who are also patients, but what about nonclinical relationships where there are not always parallels to the standards of clinical medicine? One way to treat sex in nonclinical research relationships is to treat it as sex is treated elsewhere among adults, (...) as a matter of individual choice and responsibility. Alternately, one could ask oversight bodies to draw lines between research that can safely accommodate sexual relationships and research that cannot. One could even ask researchers to avoid all concurrent sexual relationships with their research participants, as happens in clinical medicine. Each of these options has drawbacks that undermine its value as a definitive solution. The deficiencies of these options highlight the need for a professional code of conduct for nonclinical researchers. (shrink)

Developments in uterus transplant put assisted gestation within meaningful range of clinical success for women with uterine infertility who want to gestate children. Should this kind of transplantation prove routine and effective for those women, would there be any morally significant reason why men or transgender women should not be eligible for the same opportunity for gestation? Getting to the point of safe and effective uterus transplantation for those parties would require a focused line of research, over and above the (...) study of uterus transplantation for non-transgender women. Some commentators object to the idea that the state has any duty to sponsor research of this kind. They would limit all publicly-funded fertility research to sex-typical ways of having children, which they construe as the basis of reproductive rights. This objection has no force against privately-funded research, of course, and in any case not all social expenditures are responses to ‘rights’ properly speaking. Another possible objection raised against gestation by transgender women is that it could alter the social meaning of sexed bodies. This line of argument fails, however, to substantiate a meaningful objection to gestation by transgender women because social meanings of sexed bodies do not remain constant and because the change in this case would not elicit social effects significant enough to justify closing off gestation to transgender women as a class. (shrink)

Antinatalist commentators recommend that humanity bring itself to a close, on the theory that pain and suffering override the value of any possible life. Other commentators do not require the voluntary extinction of human beings, but they defend that outcome if people were to choose against having children. Against such views, Richard Kraut has defended a general moral obligation to people the future with human beings until the workings of the universe render such efforts impossible. Kraut advances this view on (...) the grounds that we are obliged to exercise beneficence toward others and on the grounds that the goods available in human lives are morally compelling. This account ultimately succeeds in making no more than a prima facie defense of human perpetuation because considerations of beneficence could override – in some cases probably should – override any duty to perpetuate human beings. While the goods of human life may be distinctive, they cannot serve as reason-giving in regard to their own perpetuation. Ironically, the exercise of beneficence may authorize the extinction of human beings, if it becomes possible to enhance the goods available to human descendants in a way that moves them away from human nature as now given. The defense of a morally obligatory and strictly human future remains elusive, even as it becomes morally desirable to work against Fateful Catastrophes, those human-caused events that threaten to extinguish existing lives already good and enriching for their bearers. (shrink)

D. Micah Hester thinks the residency match system helps sustain the divide between the haves and the have-nots in healthcare. He believes that the match system channels talent away from the have-nots in a more or less systematic way, damaging moral values in physicians as it goes. As a way of making inroads against these effects, he has asked whether assigning medical school graduates to residencies at random would distribute talent and educational opportunity more broadly and promote desirable moral values. (...) I pointed out what I think are serious limitations of this proposal, and Hester has extended me the courtesy of a reply. Yet with that reply, I find that he has made it even more difficult to defend a lottery approach to residency assignment. (shrink)

In some areas of clinical medicine, discussions about fertility preservation are routine, such as in the treatment of children and adolescents facing cancer treatments that will destroy their ability to produce gametes of their own. Certain professional organizations now offer guidelines for people who wish to modify their bodies and appearance in regard to sex traits, and these guidelines extend to recommendations about fertility preservation. Since the removal of testicles or ovaries will destroy the ability to have genetically related children (...) later on, it is imperative to counsel transgender people seeking body modifications about fertility preservation options. Fertility preservation with transgender people will, however, lead to unconventional outcomes. If transgender men and women use their ova and sperm, respectively, to have children, they will function as a mother or father in a gametic sense but will function in socially reversed parental identities. There is nothing, however, about fertility preservation with transgender men and women that is objectionable in its motives, practices, or outcomes that would justify closing off these options. In any case, novel reproductive technologies may extend this kind of role reversal in principle to all people, if sperm and ova can be derived from all human beings regardless of sex, as has happened with certain laboratory animals. (shrink)

Some critics of same-sex marriage allege that this kind of union not only betrays the nature of marriage but that it also opens children to various kinds of harm. Same-sex marriage is objectionable, on this view, in its nature and in its effects. A view of marriage as requiring an unassisted capacity to conceive children may be respect as one idea of marriage, but this view need not be understood as marriage itself. It is not clear, in any case, why (...) government should prefer this one idealized view of marriage over other others, so long as recognition of other kinds of marriage do not stand in the way of government carrying out its core interests, such as the protection of children. The idea that children are necessarily harmed when conceived by and for same-sex couples cannot be sustained as a matter of psychological evidence or moral argument. No research shows that such children are routinely harmed or rarely-but-catastrophically. Comparative accounts of the welfare of children of same-sex couples cannot show either that children must be brought into existence only under ideal circumstances. (shrink)

An overview of the key debates in biomedical researchethics, presented through a wide-ranging selection of casestudies.

The law ordinarily recognises the woman who gives birth as the mother of a child, but in certain jurisdictions, it will recognise the commissioning couple as the legal parents of a child born to a commercial surrogate. Some commissioning parents have, however, effectively abandoned the children they commission, and in such cases, commercial surrogates may find themselves facing unexpected maternal responsibility for children they had fully intended to give up. Any assumption that commercial surrogates ought to assume maternal responsibility for (...) abandoned children runs contrary to the moral suppositions that typically govern contract surrogacy, in particular, assumptions that gestational carriers are not ‘mothers’ in any morally significant sense. In general, commercial gestational surrogates are almost entirely conceptualised as ‘vessels’. In a moral sense, it is deeply inconsistent to expect commercial surrogates to assume maternal responsibility simply because commissioning parents abandon children for one reason or another. We identify several instances of child abandonment and discuss their implications with regard to the moral conceptualisation of commercial gestational surrogates. We conclude that if gestational surrogates are to remain conceptualised as mere vessels, they should not be expected to assume responsibility for children abandoned by commissioning parents, not even the limited responsibility of giving them up for adoption or surrendering them to the state. (shrink)

The marginality of poetry in American culture has been taken for granted at least since the dawn of the modernist period, when Walt Whitman printed his first volume of poetry at his own expense. More recently, it has become an article of faith that there is a real popular audience for poetry, but somewhere else-in the East. Literary journals, the popular press, and publishers have made household names of a handful of Eastern European writers: Czeslaw Milosz, Joseph Brodsky, Zbigniew Herbert. (...) One is regaled with chestnuts about ordinary people in the Eastern bloc who care about "the Word," manuscripts passed from hand to hand, even poems preserved orally. Inevitably, the questions are revived: Where are the great American poets? Has American poetry been reduced to private confessions and personal trivia? Why is it that our poetry lacks that public, political relevance? The answer to such questions is often that we do not have the weight of History on our backs, the state oppression under which, as Milosz says, "poetry is no longer alienated," no longer "a foreigner in society," and can become more important than bread.1 But what has not surfaced in the vaunted "poetry and politics" debate is the extent to which our homage to victims of censorship everywhere has become a fetishization of totalitarianism, and a self-serving one at that. The mythology of our freedom, unbounded and unmediated, depends precisely on this other world, on what happens over there. 1. Czeslaw Milosz, The Witness of Poetry , p. 95; hereafter abbreviated WP. Bruce F. Murphy's work has appeared in the Paris Review, Pequod, and An Gael. He has completed a manuscript of poems and with Friedrich Ulfers is writing a study of Friedrich Nietzsche. (shrink)

For centuries, philosophers, political scientists, and jurists have struggled to understand the possibilities for justice and peace among a multiplicity of sovereign states. Like Dante, who sought to organize the world under the authority of the Holy Roman Empire, many theorists have tried to explain how sovereign states should be governed to ensure stability and peace in the absence of any established higher authority. Theories of World Governance traces the various conceptual approaches to world harmony from the close of the (...) Middle Ages to today. Considering the immediate problems of order in a decentralized world community, Cornelius F. Murphy, Jr., outlines what he believes are the essential long-term conditions for world peace. Covering a wide range of disciplines -- from theology and philosophy to jurisprudence, ethics, and sociology -- Murphy explores how theorists have reflected upon the necessary components of an effective global order. At the outset, the thought of Christian Europe was shaped by a belief in a natural order established by the Creator of the universe. However, with the advent of the Enlightenment, the connections between the human and the transcendent were severed. There was a movement from a theocentric understanding of the powers of the human mind to an intellectual outlook that blurred the distinctions between the divine and human. This study in the history of ideas examines the profound effects of the fundamental shift from transcendence to immanence upon the development of international theory. Murphy discusses the thought of Leibniz, Wolff, Kant, Hegel, and Phillip Allott, among others. The study concludes with an extended reflection on the importanceof a sound political philosophy to the future well-being of the global community. Possible improvements in the existing arrangements, such as reform of the United Nations, are discussed. Murphy suggests that in order for a society of sovereign states to be transformed into a world political community, human rights and self-governance within states must first be strengthened and, at the same time, individuals of all states must begin to realize their responsibilities toward the whole human family. (shrink)

The value of extending the human lifespan remains a key philosophical debate in bioethics. In building a case against the extension of the species-typical human life, Nicolas Agar considers the prospect of transforming human beings near the end of their lives into Galapagos tortoises, which would then live on decades longer. A central question at stake in this transformation is the persistence of human consciousness as a condition of the value of the transformation. Agar entertains the idea that consciousness could (...) persist in some measure, but he thinks little is to be gained from the transformation because the experiences available to tortoises pale in comparison to those available to human beings. Moreover, he thinks persisting human consciousness and values would degrade over time, being remade by tortoise needs and environment. The value available in the transformation would not, then, make the additional years of life desirable. Agar’s account does not, however, dispose of the tortoise transformation as a defensible preference. Some people might still want this kind of transformation for symbolic reasons, but it would probably be better that no human consciousness persist, since that consciousness would be inexpressible as such. Even so, it is not irrational to prefer various kinds of lifespan extension even if they involve significant modifications to human consciousness and values. (shrink)

Researchers are pursuing various ways to synthesise human male and female gametes, which would be useful for people facing infertility. Some people are unable to conceive children with their partner because one of them is infertile in the sense of having an anatomical or physiological deficit. Other people—in same sex couples—may not be individually infertile but situationally infertile in relation to one another. Segers et al have described a pathway towards synthetic gametes that would rely on embryonic stem cells, rather (...) than somatic cells. This pathway would be advantageous, they say, for same-sex couples even though it would not offer those couples 50%–50% shared genetics in their children but only 50%–25%. It is unclear, however, why this approach should be preferred morally speaking since it represents a falling off from the kind of shared genetics in children that are functionally a gold standard in parents' expectations generally. Despite raising concerns about whether genetic relatedness is necessary or sufficient as a condition of parental interest in children, Segers et al cede the sociocultural importance of that standard. If so, same-sex couples seem entitled to press a case for some measure of research priority that would offer the same level of access to that social good as everyone else. (shrink)

Some commentators speak freely about genetics being poised to change human nature. Contrary to such rhetoric, Norman Daniels believes no such thing is plausible since ‘nature’ describes characteristic traits of human beings as a whole. Genetic interventions that do their work one individual at a time are unlikely to change the traits of human beings as a class. Even so, one can speculate about ways in which human beings as a whole could be genetically altered, and there is nothing about (...) that venture that could not be deliberated in the way other high-impact questions can be evaluated. There might well come a time when it would be defensible to use genetics to change human beings as a class, in order to protect people in the face of changed environmental circumstances or to enhance existing capacities. Moreover, if one understands human nature not in an empirically descriptive way but in a metaphysical way having implications about human behavior, it can make sense to talk about de-naturing individuals through genetic changes. Even under a metaphysical conception of human nature, however, one can still imagine that people in the future might want to alter their traits in pursuit of another normative idea of a good and valuable life, and genetic modifications might function as a pathway to that change. (shrink)

What sex is permissible, if any, in non-clinical research relationships? In reply to my call for a code of conduct for non-clinical research, some commentators have called for more training in such matters, but this kind of training will not go very far without some kind of governing standards yet to be determined. It is not enough to assume that unarticulated opinions will suffice. Neither will approaches that involve even greater scrutiny over research, as if to divide research into two (...) categories: one in which sex with subjects is permissible and the other in which sex is impermissible. No practical solution to exploitation will be more important than having a code of ethics that guides decision-makers where institutional review bodies do not tread. (shrink)

This essay argues that informed consent remains desirable for both moral and practical reasons in regard to HIV testing by physicians. At the very least, respect for consent preserves patient control over treatment and affords the opportunity for education about the nature of HIV-related disorders. Nevertheless, there do appear to be circumstances under which involuntary testing may occur especially when health care workers may have become occupationally exposed to risk of HIV infection. To eliminate conflicts between health workers and their (...) patients, however, it is desirable to work to eliminate the stigmatizing and discriminatory effects of HIV infection that can induce persons to resist testing. (shrink)